Sodium hydride → (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630291Notes

Reaction equation

HRID 1630291 reaction equation
[Cl-].[F:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7]P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=[CH:5][CH:4]=1.[H-].[Na+].[N:31]1([CH2:36][C:37]([N:39]2[CH2:43][C:42](=O)[CH2:41][C@H:40]2[C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][C:55]3[CH:60]=[CH:59][C:58]([F:61])=[CH:57][CH:56]=3)=[CH:50][CH:49]=2)=[O:46])=[O:38])[CH:35]=[N:34][CH:33]=[N:32]1>CS(C)=O>[N:31]1([CH2:36][C:37]([N:39]2[CH2:43][C:42](=[CH:7][C:6]3[CH:5]=[CH:4][C:3]([F:2])=[CH:28][CH:27]=3)[CH2:41][C@H:40]2[C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([O:54][C:55]3[CH:56]=[CH:57][C:58]([F:61])=[CH:59][CH:60]=3)=[CH:50][CH:49]=2)=[O:46])=[O:38])[CH:35]=[N:34][CH:33]=[N:32]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 56954158(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamideHCID 178505801HCID 178505801, compound

Product 1

HCID 67009559(S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamideYield 11%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent3×

Conditions

Temperature
70 °C

Procedure

Step (b) 4-Fluorobenzyl triphenylphosphine chloride (1 g, 2.46 mmol) in DMSO (2 mL) was added to a flask charged with sodium hydride (60% dispersion in oil, 124 mg, 3.10 mmol) and DMSO (2 mL). The reaction mixture was stirred at 70° C. for 3 hours and then (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-oxopyrrolidine-2-carboxamide (0.11 g, 0.25 mmol) in DMSO (2 mL) was added. The mixture was stirred for 16 hours at 70° C. and then quenched with saturated ammonium chloride (aq., 10 mL). This mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL). Product was purified from the mixture directly by column chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give with (S)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-(4-fluorobenzylidene)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (15 mg, 0.027 mmol, 11% yield) as an oil.

Workup

  1. stirringThe mixture was stirred for 16 hours at 70° C.
  2. customquenched with saturated ammonium chloride (aq., 10 mL)
  3. extractionThis mixture was extracted with ethyl acetate (20 mL)
  4. washthe extract was washed with deionized water (10 mL)
  5. customProduct was purified from the mixture directly by column chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

Sources & evidence

ORD record
ord-52204468990848df8fcaee1c8dbe1907
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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